TNF and Cowden disease: In our study, the data analysis shows that the rare gain-of-function frameshift variant (c.1143_1144insG; p. Leu381_Leu382fs) in SIRPB1 is associated with Han Chinese patients with CD and provides insights that the variant in SIRPB1 upregulated the activation of NF-κB and increased the production of IL-1β, TNF-α, and IL-6 by inducing DAP12, Syk, Akt, and Jak2 to become tyrosine phosphorylated in macrophages, CD pathogenesis is facilitated.